Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute on Deafness and Other Communication Disorders (NIDCD)
Funding Opportunity Title	NIDCD Phase I/II/III Clinical Trials in Communication Disorders (U01)
Activity Code	U01 Research Project Cooperative Agreements
Announcement Type	New
Related Notices	February 10, 2015 - This PA has been reissued as PAR-15-116. August 7, 2014 - See Notice NOT-DC-14-004. June 3, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same. October 18, 2013 - See Notice NOT-OD-14-003. Guidance on Resumption of NIH Extramural Activities Following the Recent Lapse in Appropriations. May 30, 2013 (NOT-OD-13-074) - NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013. Forms-C applications are required for due dates on or after September 25, 2013. March 5, 2013 - See Notice NOT-DC-13-002. New NIDCD Clinical Trials Policy on Post-Submission Application Materials. March 23, 2012 - See Notice NOT-DC-12-008. Notice of Replacement of NIDCD Clinical Trial Funding Opportunity Announcements.
Funding Opportunity Announcement (FOA) Number	PAR-12-123
Companion FOA	PAR-12-124, NIDCD Planning Grant for Phase III Clinical Trials in Communication Disorders (U34)
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.173
FOA Purpose	The NIDCD is committed to identifying effective interventions for the treatment or prevention of communication disorders by supporting robust, well-designed, and well-executed clinical trials. This funding opportunity announcement (FOA) supports a cooperative agreement between NIDCD project collaborator and investigator to support phase I and II clinical trials of preliminary efficacy and phase III clinical trials of definitive efficacy. Phase III clinical trial applications must include a complete detailed Manual of Procedures (MOP) in the appendix (see http://www.nidcd.nih.gov/research/clinicaltrials for an example of a complete, detailed MOP). The NIDCD Planning Grant for Phase III Clinical Trials in Communication Disorders (U34) (PAR-12-124) may be used to gather information and prepare the MOP.

Posted Date	March 16, 2012
Open Date (Earliest Submission Date)	May 4, 2012
Letter of Intent Due Date	30 days before planned submission date.
Application Due Date(s)	June 4, 2012; October 4, 2012; February 4, 2013; June 4, 2013; (Extended to November 1, 2013 per NOT-OD-14-003), Originally October 4, 2013,February 4, 2014; June 4, 2014; October 3, 2014; February 4, 2015 , by 5:00 PM local time of applicant organization.
AIDS Application Due Date(s)	Not Applicable.
Scientific Merit Review	Standard Dates apply
Advisory Council Review	Standard Dates apply
Earliest Start Date(s)	Standard dates apply
Expiration Date	February 5, 2015
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

This announcement is part of the NIDCDs clinical research program in communication disorders (hearing, balance, taste, smell, voice, speech and language) with the goal of producing research findings that have significant clinical use and public health impact through the design and implementation of phase III clinical trials. Phase I and II clinical trials provide data that are necessary to address core scientific, design, and clinical issues prior to the conduct of the phase III clinical trial.

Phase I Clinical Trials

Phase I clinical trials test a new biomedical or behavioral intervention in a small group of people for the first time to determine efficacy and evaluate safety (e.g., determine a safe dosage range and identify side effects), in anticipation of a phase II clinical trial of preliminary efficacy. The phase I research application should directly address how the phase I study will guide the development of subsequent phase II and III clinical trials.

Relevant phase I research topics include, but are not limited to the following:

• Studies to optimize the intervention strategy (e.g. dose, duration, frequency of dosing or treatment)
• Studies to assess the appropriate delivery system or parameter settings of an electronic device or surgical technique or behavioral intervention
• Studies to assess the safety and tolerability at various doses or concentrations of a biologic intervention
• Studies to evaluate whether there is sufficient evidence of short-term improvement in humans to justify an efficacy trial
• Studies designed to select the best of 2 or more potential behavioral interventions or dosing regimens
• Studies to identify inclusion and exclusion criteria

Some aspects of feasibility and study mechanics may also be addressed as secondary objectives. Examples of these secondary objectives include the following:

• Determining the optimal outcome evaluation measure, its variability, and the optimal timing of outcome evaluations in the context of the intervention
• Collecting or developing information about potential surrogate outcome measures, questionnaires, or rating scales
• Developing and refining data collection procedures
• Developing and refining standardized methods of assessing outcome
• Evaluating whether clinicians can correctly administer the study intervention
• Determining the best methods for identifying and recruiting study subjects

Phase II Clinical Trials

Phase II clinical trials study the biomedical or behavioral intervention in a larger group of people to determine preliminary efficacy and further evaluate safety, in anticipation of a phase III clinical trial of definitive efficacy. The phase II clinical trial should collect and develop essential preliminary information rather than simply address the clinical question with lower power, i.e. a phase II trial should not simply be a miniature version of a phase III trial.

Basic elements of the phase II clinical trial application should include identification of the patient population; inclusion and exclusion criteria; adequate plans for recruitment and retention of participants; experimental design and protocols; clear definition of the research hypothesis and outcome measures; quality control/assurance procedures; analytical techniques; sample size estimates with justification; administrative procedures (including regulatory approvals if necessary); collaborative arrangements; duties and responsibilities of study chairperson, clinical sites, coordinating centers, and other central resource centers such as a central laboratory or radiographic center; and monitoring plans to assure patient protection and data integrity. Also see Section V. Application Review Information, Significance, Investigators and Approach.

Phase III Clinical Trials

Phase III clinical trials determine efficacy of the biomedical or behavioral intervention in large groups of people by comparing the intervention to other standard or experimental interventions as well as to monitor adverse effects, and to collect information that will allow the interventions to be used safely. Basic elements of the phase III clinical trial application are similar to those of phase II clinical trials, described above. Also see Section V. Application Review Information, Significance, Investigators and Approach.

Phase III clinical trial applications must include a complete detailed Manual of Procedures (MOP) in the appendix (see http://www.nidcd.nih.gov/research/clinicaltrials for an example of a complete, detailed MOP). The NIDCD Planning Grant for Phase III Clinical Trials in Communication Disorders (U34) (PAR-12-124) may be used to gather information and prepare the MOP.

Each phase III definitive clinical trial must have a Study Chair who is responsible for the overall development and conduct of the trial and provides both the scientific and administrative leadership for the trial; a Clinical Coordinating Center that provides overall coordination for the clinical trial to ensure data quality, conformance to implementing the MOP, quality assurance, statistical analyses, and assistance with preparing publications; a Data Coordinating Center for design and implementation of data forms, and for data entry, management and integrity; and Clinical Centers that are responsible for implementing the protocol, recruiting patients, providing the intervention/prevention required, conducting patient follow up, and submitting data to the Data Coordinating Center.

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Funding Instrument	Cooperative Agreement
Application Types Allowed	New Resubmission Revision The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications.
Award Budget	Application budgets are not limited, but must reflect actual needs of the proposed project. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plan of the NIDCD provides support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds. Facilities and Administrative (F&A) costs requested by consortium participants are not included in the direct cost, see NOT-OD-05-004.
Award Project Period	Up to five years

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

• Central Contractor Registration (CCR) must maintain an active registration, to be renewed at least annually
• Grants.gov
• eRA Commons

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 4-6 weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PD(s)/PI(s), visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed research
• Name, address, and telephone number of the PD(s)/PI(s)
• Names of other key personnel
• Participating institutions
• Number and title of this funding opportunity

The letter of intent should be sent to:

Gordon B. Hughes, M.D.
Director Clinical Trials Program, Division of Scientific Programs
National Institute on Deafness and Other Communication Disorders, NIH
6120 Executive Blvd.
EPS-400C MSC 7180
Bethesda, MD 20892-7120
Telephone: (301) 496-5061
Fax: (301) 402-6251
Email:[email protected]

The forms package associated with this FOA includes all applicable components, mandatory and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

If an NIDCD phase III clinical trial planning grant was awarded, then the phase III clinical trial applicant should include in the Preliminary Studies for New Applications section a brief summary of the activities achieved during the planning period. Regardless of whether a planning grant was used first, all phase III clinical trial applications must have a complete, detailed Manual of Procedures (MOP) included as an Appendix (see http://www.nidcd.nih.gov/research/clinicaltrials for an example of a complete, detailed MOP).

For phase III clinical trial applications, sections within the MOP should describe details of the operations of the Study Chair, Clinical Coordinating Center, Data Coordinating Center, and Clinical Centers. In describing the different aspects of the phase III clinical trial in the body of the application to address the review criteria (see Section V.1 Significance, Investigators and Approach), the applicant should refer to appropriate sections in the MOP to provide peer reviewers with complete details; however, all required application pieces must be contained within the application proper. The MOP should not be used to circumvent application page limits.

Single-site phase I and II clinical trial applications should be submitted as one application.

Multi-site phase I and II clinical trial applications should be submitted as two paired applications from the Study Chair/Clinical Coordinating Center and the Data Coordinating Center. Individual Clinical Centers should be subcontracts to the Study Chair/Clinical Coordinating Center. This information must be clearly communicated to NIDCD prior to submission as well as in a cover letter at the time of submission, to ensure correct assignment by Division of Receipt and Referral.

All phase III clinical trial applications should be submitted as two paired applications from the Study Chair/Clinical Coordinating Center and the Data Coordinating Center. Individual Clinical Centers should be subcontracts to the Study Chair/Clinical Coordinating Center. The MOP must be an Appendix to the Study Chair/Clinical Coordinating Center application.

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modifications:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. The NIDCD asks that all phase I, II and III clinical trials be registered in ClinicalTrials.gov. The FDA requires that all phase II and III clinical trials with IND or IDE be registered in ClinicalTrials.gov. Publications related to the clinical trial must be published in NIH PubMed Central.

Appendix

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide. For this clinical trial Funding Opportunity Announcement, the following documents may be submitted in the Appendix as necessary:

• questionnaires
• data collection instruments
• clinical protocols
• informed consent documents
• Investigator Brochure for an Investigational Device Exemption (IDE) or Investigational New Drug (IND)
• In phase III clinical trial applications, the above should be included directly in the MOP.

Foreign (non-US) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via Grants.gov, the online portal to find and apply for grants across all Federal agencies. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

Applicants are responsible for viewing their application in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF 424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(R&R) Application Package. Failure to register in the Commons and to include a valid PD(s)/PI(s) Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the Central Contractor Registration (CCR). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Concept Proposal

Applicants are strongly encouraged but are not required to submit a clinical trial concept document to the NIDCD for programmatic review prior to submitting an application in response to this FOA. For information on the NIDCDs Clinical Trial Concept Procedure see Clinical Trials on NIDCDs website at http://www.nidcd.nih.gov/research/clinicaltrials.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

In order to expedite review, applicants are requested to notify the NIDCD Referral Office by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD(s)/PI(s) name, and title of the application.

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact NIH program staff at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF 424 (R&R) Application Guide.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Does the applicant address the following:

• A clear statement of the questions(s) that the trial will address and its importance;
• Information adequate to determine the significance and timeliness of as well as the need to perform the trial;
• Preliminary data or the literature supporting the need for a clinical trial to test the proposed hypothesis or intervention;
• Reasons for selection of the intervention, study agent(s), and mode of delivery including specific details such as dose or a particular procedure; and,
• The ethical issues surrounding the trial and the disease/condition under study?

Investigators

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PDs/PIs, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Does the application describe the leadership and proposed organization of the clinical trial PD(s)/PIs/Study Chair have the experience to provide the leadership and management to the clinical trial network? Do the clinical site PDs/PIs have experience in running a clinical site and/or clinical trial experience and in successfully recruiting and retaining patients in a research study? Does the Director of the Clinical Coordinating Center have prior clinical trial experience and experience in managing a coordinating center for a multicenter clinical trial? Does the Data Coordinating Center have the appropriate expertise?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

For phase I and II clinical trials, how likely is it that the proposed design will eventually lead to a phase III clinical trial? What is the importance of the preliminary clinical trial to the eventual success of the phase III definitive clinical trial? What is the importance of the phase III clinical trial?

Is the experimental design adequate and does it address the following (as applicable):

• Translation of the clinical question into a statistical hypothesis;
• Primary and secondary outcome variable(s) and data to be collected, including relevance to the clinical and statistical hypothesis being tested;
• Criteria for evaluating outcome variable(s);
• Sample size and duration of the trial;
• Randomization if needed, masking if appropriate, controls, and inclusion/exclusion criteria;
• Plans to standardize and monitor adherence to the clinical protocol;
• Interim data monitoring if appropriate;
• Plans to obtain any required study agent;
• Methods for standardization of procedures for data management to assess the effect of the intervention and quality control; and,
• Appropriateness of the general statistical approach and specific analytic techniques and plans for handling dropouts, missed visits, and losses to follow up?

Does the application document the following related to patient recruitment/retention (as applicable):

• Availability of the requisite eligible subject pool;
• Plans for recruitment outreach and, as appropriate, follow-up procedures to ensure collection of data at stated intervals;
• Retention plans and practices; and,
• Criteria for withdrawal?

Is the safety monitoring plan adequate and does it address the following:

• Risks involved;
• Ethical aspects of risks
• Risk-benefit balance;
• Informed consent procedures; and,
• Provisions for early termination?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not Applicable.

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact/priority score.

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NIDCD, in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact/priority score.
• Will receive a written critique.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications.. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

After the peer review of the application is completed, the PD(s)/PI(s) will be able to access his or her Summary Statement (written critique) via the eRA Commons.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• All aspects of the study, including any modification of study design, conduct of the study quality control, data analysis and interpretation, preparation of publications, dissemination of data, tools, and technologies, and collaboration with other investigators. The awardee agrees to accept close coordination, cooperation, and participation of NIDCD staff in those aspects of scientific and technical management of the study as stated in these terms and conditions commensurate with the degree of potential risk to study subjects and the complexity of the study.
• Upon implementation of the protocol, each field center, whether a single institution or a consortium of institutions, will follow the procedures required by the protocol regarding study conduct and monitoring, patient management, data collection, and quality control;
• Managing involvement of industry or any other third party in the study. Except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by the NIDCD; and
• Making all study materials and procedure manuals available in the public domain. Awardees are expected to publish and publicly disseminate results, data, and other products of the study, concordant with governance policies and protocols. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of support by the NIDCD/NIH.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

NIH staff has substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• Have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports. NIDCD staff may use information obtained from the data for the preparation of internal reports on the activities of the study. However, awardees will retain custody of and have primary rights to all data developed under these awards, subject to Government rights of access consistent with HHS, PHS, and NIH policies;
• Provide guidance and support in the development, assembly, and submission of all required regulatory documents, e.g., those regarding the use of investigational drugs, to the Food and Drug Administration;
• Serve as a resource to provide scientific/programmatic support during the accomplishment of the research by participating in the design of the activities, advising in the selection of sources or resources (e.g., determining where a particular reagent can be found), provision of research resources and reagents available from the NIDCD grantees and contractors, advising in management and technical performance, or participating in the preparation of publications;
• Review the progress of the study, and of each participating facility, through consideration of the annual reports, site visits, patient logs, etc. This review may include, but is not limited to, compliance with the study protocol, meeting patient enrollment targets, adherence to uniform data collection procedures, and the timeliness and quality of data reporting;
• Oversee the adequacy of adverse event management and reporting, and have regular communications with the PD(s)/PI(s) and study team, which may include attendance at the safety monitoring (or DSMB) and related committee meetings;
• Monitor progress of study milestones. At each scheduled interim review, compare actual enrollment to the benchmarks and criteria identified in the application and negotiated prior to award.

Studies in which recruitment milestones are not met as per criteria established pre-award, or for which regulatory approval has not been met within one year, and are deemed unlikely to improve sufficiently to bring the study to completion within an acceptable budget or time frame, may be closed for lack of progress following review and consideration by NIDCD staff.

If a study is finally determined to lack feasibility and will no longer accrue subjects, awardees are required to submit a close-out plan to NIDCD staff within three months of a decision either by NIDCD staff or the grantee that an awarded study is no longer feasible. The plan must be approved and signed by the Institutional Official and the PI/PD(s) listed on the award prior to submission.

The NIDCD may terminate or curtail the study (or an individual award) in the event of (a) failure to implement the study protocol, (b) a substantial shortfall in participant recruitment, follow-up, data reporting and dissemination, quality control, or other major breach of the protocol, (c) substantive changes in the agreed-upon protocol with which the NIDCD does not concur, (d) reaching a major study objective substantially before schedule with persuasive statistical evidence, or (e) human subject ethical issues that may dictate a premature termination.

Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

• Data Safety and Monitoring Board: An independent Data and Safety Monitoring Board will be established jointly by the PD(s)/PI(s) and NIDCD. The Data and Safety Monitoring Board will review interim results periodically as established in the data and safety monitoring plan and report to the NIDCD Program Director. The NIDCD Program Director will report in writing to the PD(s)/PI(s) on the recommendations of the DSMB and the NIDCD concurrence/non-concurrence of the DSMB recommendations. The PD(s)/PI(s) will assume responsibility for reporting of the DSMB and the NIDCD recommendations to their Institutional Review Board.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the PD(s)/PI(s), chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Prior consultation from NIDCD is strongly encouraged for submission of the NIDCD Phase I/II/III Clinical Trials in Communication Disorders (U01) grant application, including new and resubmission applications. Staff will consider whether the proposed clinical trial meets the goals and mission of the Institute and whether it is appropriate to conduct it as an investigator-initiated clinical trial. In the presubmission consultative phase, if the proposed trial does not meet the goals and mission of NIDCD, applicants will be strongly encouraged to look at other funding opportunities, OR applicants will be informed that the proposed trial does not meet the goals and mission of NIDCD.

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
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Gordon B. Hughes, M.D.
Director Clinical Trials Program, Division of Scientific Programs
National Institute on Deafness and Other Communication Disorders, NIH
6120 Executive Blvd.
EPS-400C MSC 7180
Bethesda, MD 20892-7180
Telephone: (301) 496-5061
Fax: (301) 402-6251
Email: [email protected]

Melissa Stick, Ph.D., MPH
Chief Scientific Review Branch, Division of Extramural Activities
National Institute on Deafness and Other Communication Disorders, NIH
6120 Executive Blvd.
EPS-400C MSC 7180
Bethesda, MD 20892-7180
Telephone: (301) 496-8683
Fax: (301) 402-6250
Email: [email protected]

Mr. Christopher Myers
Chief Grants Management, Division of Extramural Activities
National Institute on Deafness and Other Communication Disorders, NIH
EPS-400B MSC 7180
6120 Executive Blvd.
Bethesda, MD 20892-7180
Telephone: (301) 435-0713
Fax: (301) 451-5370
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.